Positron-emission tomography/computed tomography (PET/CT) imaging with the prostate-specific membrane antigen (PSMA)-targeted radiotracer fluorine F-18 DCFPyL (PyL) successfully identified areas of occult metastasis in men with biochemically recurrent metastatic castration-resistant prostate cancer. This type of imaging led to management changes in about two-thirds of participants in the CONDOR trial. These results were presented during the ASCO20 Virtual Scientific Program.¹

CONDOR is the second trial to confirm the diagnostic superiority of PyL–PET/CT to conventional imaging. OSPREY was the first to do so, in the setting of high-risk localized disease and radiographically recurrent disease.² ­CONDOR’s focus was on men who had biochemically relapsed after undergoing definitive local therapy, but who had uninformative or equivocal standard imaging studies. Both trials were initiated to support the regulatory approval of PSMA-directed PET in the United States.

“CONDOR met and even well exceeded its primary endpoint, showing that PyL–PET/CT has excellent diagnostic performance in men with biochemically relapsed prostate cancer, even at low levels of PSA [prostate-specific antigen]. The study shows that PyL–PET/CT is superior to standard imaging in men with biochemically recurrent prostate cancer and that the results yielded actionable information that is clinically significant,” stated Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, New York.

Michael J. Morris, MD

“Optimized treatment patterns need to be further defined. This trial, coupled with the OSPREY study, have now established the performance characteristics of PyL–PET/CT in localized biochemically recurrent and metastatic prostate cancer,” Dr. Morris stated.

Originally, the data from CONDOR were planned as two separate presentations—one for the primary endpoint of diagnostic performance, and the second for the impact of imaging results on management of patients in the trial. Both abstracts were pooled as one presentation once the ASCO20 virtual meeting was planned.

Background

Current imaging modalities are inadequate for localizing and characterizing occult disease in men with biochemically recurrent prostate cancer, particularly in patients with low PSA levels (< 2 ng/mL). There is a need for improved diagnostic imaging to better inform treatment planning.

Several types of PSMA-targeted imaging are under study in hopes of improving diagnostic accuracy. CONDOR focused on PyL-PET-CT in men with metastatic castration-resistant prostate cancer.

PyL is a lysine-linked, urea-based small molecule and novel PET imaging agent that binds selectively with high affinity to PSMA, which is overexpressed in prostate cancer cells. PyL-PET imaging is conducted 1 to 2 hours following administration of a single dose of PyL.

Study Details

CONDOR enrolled 208 men aged 18 years or older with a rising PSA level after definitive therapy and negative or equivocal standard-of-care imaging (eg, CT, magnetic resonance imaging [MRI], bone scintigraphy). A PSA level of 0.2 ng/mL was required for those who had undergone radical prostatectomy and a PSA level > 2 ng/mL for those treated with prior systemic therapy. All patients had biochemically recurrent metastatic castration-resistant prostate cancer. All patients had no previous radiologic findings. The objective of the first part of the study was to detect occult disease.

Diagnostic performance was assessed using correct localization rate, “a term proposed by [the U.S. Food and Drug Administration] for positive predictive value with the added requirement of anatomic location matching,” Dr. Morris said. “An anatomic atlas was created prior to the study to provide a consistent reference for anatomical location matching across imaging modalities.”

Correct localization rate was defined as the percentage of patients with a 1:1 correspondence between at least one lesion identified by PyL–PET/CT and the composite “standard of truth”: pathology, correlative imaging, or PSA response. The trial was considered successful if the lower bound of the 95% confidence interval for correct localization rate exceeded 20% for two of three independent, blinded central PyL–PET/CT reviewers. 

After meeting eligibility requirements, clinicians completed questionnaires both preimaging and postimaging about intended management of each patient. PyL scans were read by three blinded independent readers.

CONDOR was conducted at 14 sites in the United States and Canada. Eighty-five percent of the study population underwent radical prostatectomy alone or with radiation. “The PSA values were representative of this population, and median PSA was quite low, at 0.8 ng/mL, although there were some outliers,” Dr. Morris said. About half the patients had a PSA level < 1 ng/mL, and 70% had a PSA level < 2 ng/mL, “which are PSA ranges in which most decisions about subsequent salvage focal or systemic therapies are made,” he noted.

The correct localization rate or positive predictive value was excellent—89%, 87%, and 84% for the three readers, respectively. “This was well in excess of the 20% benchmark we had set,” Dr. Morris said.

“The robust performance of [correct localization rate] was maintained regardless of PSA values. PyL detected disease even at the lowest of PSA values,” he stated.

Changes in Management

For the secondary endpoint of impact on treatment, 64% of patients had a change in management due to PSMA-PET findings. Of them, 78% were attributable to positive findings, and 21.4% to negative PyL scans.

Specific changes included the following:

• 21% had their goal changed from noncurative to curative salvage local therapy.
• 28% changed from salvage local therapy to systemic therapy.
• 23.9% changed from observation to initiation of therapy.
• 4.4% downgraded from planned treatment to observation.

PyL was associated with no significant safety issues. The radiotracer was well tolerated, with one drug-related serious adverse event (hypersensitivity); the most common adverse event was headache, reported in four patients (1.9%). 

DISCLOSURE: CONDOR was funded by Progenics. Dr. Morris has served in a consulting or advisory role for Advanced Accelerator Applications, Astellas Pharma, Bayer, Blue Earth Diagnostics, Endocyte, ORIC Pharmaceuticals, Tokai Pharmaceuticals, and Tolmar Pharmaceuticals; has received institutional research funding from Bayer, Corcept Therapeutics, Endocyte, Progenics, Roche/Genentech, and Sanofi; and has been reimbursed for travel, accommodations, or other expenses from Bayer and Endocyte.

REFERENCES

1. Morris MJ, Carroll PR, Saperstein L, et al: Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients with biochemically recurrent prostate cancer: Results from a phase III prospective, multicenter study (CONDOR). ASCO20 Virtual Scientific Program. Abstract 5501.

2. Rowe S, Gorin M, Pienta K, et al: Results from the OSPREY trial: A prospective phase 2/3 multi-center study of 18F-DCFPyL PET/CT imaging in patients with prostate cancer: Examination of diagnostic accuracy. J Nucl Med 60(suppl 1):586, 2019.